An alanyl-alanyl-phenylalanyl-7-amino-4-methylcoumarin-hydrolyzing protease
particle copurifying with 265 proteasomes was isolated and identified as t
ripeptidyl peptidase II(TPPII), a cytosolic subtilisin-like peptidase of un
known function. The particle is larger than the 265 proteasome and has a ro
d-shaped, dynamic supramolecular structure. TPPII exhibits enhanced activit
y in proteasome inhibitor-adapted cells and degrades polypeptides by exo- a
s well as predominantly trypsin-like endoproteolytic cleavage. TPPII may th
us participate in extralysosomal polypeptide degradation and may in part ac
count for nonproteasomal epitope generation as postulated for certain major
histocompatibility complex class I alleles, In addition, TPPII may be able
to substitute for some metabolic functions of the proteasome.